Search

Aim: To examine the relationship between preterm birth and hospitalisation for paediatric complex chronic conditions., Methods: We conducted a cohort study of 1 269 745 children born between 2006 and 2022 in Quebec, Canada. We classified preterm birth as extreme (<28 weeks), very (28-31 weeks), and moderate (32-36 weeks). The outcome was hospitalisation for complex chronic conditions, including neurologic, neuromuscular, cardiovascular, respiratory, renal, gastrointestinal, haematologic, immunologic, endocrine, and neoplastic disorders up to 16 years of age. We computed adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between preterm birth and complex chronic conditions during 9 948 734 person-years of follow-up., Results: Hospitalisation rates for complex chronic conditions were higher for children born preterm than at term (6.88 vs. 2.24 per 1000 person-years). Preterm birth was associated with all complex chronic conditions, especially respiratory (HR 4.64, 95% CI 4.01-5.37), cardiovascular (HR 3.68, 95% CI 3.47-3.90), and neurologic disorders (HR 3.48, 95% CI 3.21-3.77). Associations were present at all ages and for all degrees of prematurity, but were strongest with extreme prematurity., Conclusion: Preterm birth increases the risk of hospitalisation for complex chronic conditions up to age 16 years. Preterm children may benefit from enhanced care throughout childhood and adolescence., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

We assessed the impact of the COVID-19 pandemic on the pregnancy outcomes of patients who used assisted reproductive technology. We conducted a population-based cohort study of 443,101 patients who conceived naturally or with assisted reproductive technology between December 2015 and July 2021 and had a delivery in hospitals of Quebec, Canada. The main exposure measure was use of assisted reproductive technology before or during the pandemic. Outcomes included preeclampsia, preterm birth, and other pregnancy complications. We used adjusted log-binomial regression models to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association of assisted reproductive technology with adverse pregnancy outcomes compared with natural conception before vs. during the pandemic. In secondary analyses, we examined the association of COVID-19 infection with pregnancy outcomes among women who used assisted reproductive technology. Compared with natural conception, assisted reproductive technology was associated with an increased risk of preeclampsia (RR 1.43; 95% CI 1.21-1.68), preterm birth (RR 2.07; 95% CI 1.84-2.33), and low birth weight (RR 1.94; 95% CI 1.72-2.20) during the pandemic. However, the same risks were also present before the pandemic. Compared with no infection, COVID-19 infection was not associated with adverse outcomes among women who conceived with assisted reproductive technology. This study suggests that the COVID-19 pandemic did not significantly impact the pregnancy outcomes of women who underwent assisted reproductive procedures in Quebec. The findings are reassuring for patients concerned about the potential reproductive effects of the pandemic., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Aim: To co-create parental presence practice recommendations across Canadian NICUs during pandemics caused by respiratory pathogens such as COVID-19., Methods: Recommendations were developed through evidence, context, Delphi and Values and Preferences methods. For Delphi 1 and 2, participants rated 50 items and 20 items respectively on a scale from 1 (very low importance) to 5 (very high). To determine consensus, evidence and context of benefits and harms were presented and discussed within the Values and Preference framework for the top-ranked items. An agreement of 80% or more was deemed consensus., Results: After two Delphi rounds ( n  = 59 participants), 13 recommendations with the highest rated importance were identified. Consensus recommendations included 6 strong recommendations (parents as essential caregivers, providing skin-to-skin contact, direct or mothers' own expressed milk feeding, attending medical rounds, mental health and psychosocial services access, and inclusion of parent partners in pandemic response planning) and 7 conditional recommendations (providing hands-on care tasks, providing touch, two parents present at the same time, food and drink access, use of communication devices, and in-person access to medical rounds and mental health and psychosocial services)., Conclusion: These recommendations can guide institutions in developing strategies for parental presence during pandemics caused by respiratory pathogens like COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Campbell-Yeo, Bacchini, Alcock, Mitra, MacNeil, Mireault, Beltempo, Bishop, Campbell, Chilcott, Comeau, Dol, Grant, Gubbay, Hughes, Hundert, Inglis, Lakoff, Lalani, Luu, Morton, Narvey, O'Brien, Robeson, Science, Shah and Whitehead.)

Aim: Parents of children born preterm have identified outcomes to be measured for audit and research at 18-24 months of age: child well-being, quality of life/function, socio-emotional/behavioural outcomes, respiratory, feeding, sleeping, and caregiver mental health. The aim was to identify the best tools to measure these seven domains., Methods: Seven working groups completed literature reviews and evaluated potential tools to measure these outcomes in children aged 18-24 months. A group of experts and parents voted on the preferred tools in a workshop and by questionnaire. Consensus was 80% agreement., Results: Consensus was obtained for seven brief, inexpensive, parent friendly valid measures available in English or French for use in a minimum dataset and potential alternative measures for use in funded research., Conclusion: Valid questionnaires and tools to measure parent-identified outcomes in young preterm children exist. This study will facilitate research and collection of data important to families., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Infections in the first trimester of pregnancy can be teratogenic, but the possibility that Covid-19 could lead to birth defects is unclear. We examined whether SARS-CoV-2 infection during pregnancy or exposure to pandemic conditions were associated with the risk of congenital anomalies. We carried out a retrospective study of 420,222 neonates born in Quebec, Canada in two time periods: prepandemic (January 1, 2017 to March 12, 2020) vs. pandemic (March 13, 2020 to March 31, 2022). We classified pandemic births as early (first trimester completed before the pandemic) or late (first trimester during the pandemic), and identified patients with SARS-CoV-2 infections during pregnancy. We applied (1) adjusted log-binomial regression models to assess the association between SARS-CoV-2 infection and congenital anomalies, and (2) autoregressive interrupted time series regression to analyze temporal trends in the monthly number of defects in all patients regardless of infection. In total, 29,263 newborns (7.0%) had a congenital anomaly. First trimester SARS-CoV-2 infections were not associated with a greater risk of birth defects compared with no infection (RR 1.07, 95% CI 0.59-1.95). However, births during the late pandemic period were more likely to be diagnosed with congenital microcephaly compared with prepandemic births (RR 1.44, 95% CI 1.21-1.71). Interrupted time series analysis confirmed that the frequency of microcephaly increased during the late pandemic period, whereas other anomalies did not. We conclude that Covid-19 is likely not teratogenic, but enhanced surveillance of anomalies among late pandemic births may have heightened the detection of infants with microcephaly., (© 2024. Springer Nature B.V.)

Individuals born preterm present lower exercise capacity. Along with the cardiopulmonary responses and activity level, muscle strength is a key determinant of exercise capacity. This systematic review aimed to summarize the current knowledge on the impact of preterm birth on skeletal muscle mass and function across the lifespan. The databases PubMed, MEDLINE, EBM, Embase, CINAHL Plus, Global Index Medicus, and Google Scholar were searched using keywords and MeSH terms related to skeletal muscle, preterm birth, and low birth weight. Two independent reviewers undertook study selection, data extraction, and quality appraisal using Covidence review management. Data were pooled to estimate the prematurity effect on muscle mass and function using the R software. From 4378 studies retrieved, 132 were full-text reviewed and 25 met the inclusion/exclusion criteria. Five studies presented a low risk of bias, and 5 had a higher risk of bias due to a lack of adjustment for confounding factors and presenting incomplete outcomes. Meta-analyses of pooled data from homogenous studies indicated a significant reduction in muscle thickness and jump test (muscle power) in individuals born preterm versus full-term with standardized mean difference and confidence interval of - 0.58 (0.27, 0.89) and - 0.45 (0.21, 0.69), respectively.    Conclusion: Overall, this systematic review summarizing the existing literature on the impact of preterm birth on skeletal muscle indicates emerging evidence that individuals born preterm, display alteration in the development of their skeletal muscle mass and function. This work also highlights a clear knowledge gap in understanding the effect of preterm birth on skeletal muscle development. What is Known: • Preterm birth, which occurs at a critical time of skeletal muscle development and maturation, impairs the development of different organs and tissues leading to a higher risk of comorbidities such as cardiovascular diseases. • Preterm birth is associated with reduced exercise capacity. What is New: • Individuals born preterm display alterations in muscle mass and function compared to individuals born at term from infancy to adulthood. • There is a need to develop preventive or curative interventions to improve skeletal muscle health in preterm-born individuals., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To examine the association between maternal hypertension during pregnancy and neurodevelopmental impairment (NDI) at 24 months post-menstrual age in extremely preterm infants., Study Design: Using data from two tertiary neonatal units (2011-2017) for infants born at 23 + 0 to 28 + 6 weeks, we investigated outcomes of NDI related to maternal hypertension and small-for-gestational-age (SGA) status., Results: Of 1019 pre-term infants, 647 had complete data and were included in the analysis. Ninety-six (15%) had maternal hypertension exposure; 25 (4%) were also SGA. Infants with maternal hypertension showed a higher odds of any NDI (aOR: 2.29, 95% CI = 1.36-3.87) and significant NDI (aOR: 2.01, 95% CI = 1.02-3.95). The combination of hypertension and SGA further elevated this risk (aOR for any NDI: 4.88, 95% CI = 1.80-13.22; significant NDI: 6.91, 95% CI = 2.50-19.12)., Conclusion: Maternal hypertension during pregnancy elevates the risk of NDI in extremely preterm infants, more so when combined with SGA., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: Assess if unit-level PDA management correlates with neurodevelopmental impairment (NDI) at 18-24 months corrected postnatal age (CPA) in extremely preterm infants., Study Design: Retrospective analysis of infants born at <29 weeks (2014-2017) across two units having distinct PDA strategies. Site 1 utilized an echocardiography-based treatment strategy aiming for accelerated closure (control). Site 2 followed a conservative approach., Primary Endpoint: NDI, characterized by cerebral palsy, any Bayley-III composite score <85, sensorineural/mixed hearing loss, or at least unilateral visual impairment., Results: 377 infants were evaluated. PDA treatment rates remained unchanged in Site 1 but eventually reached 0% in Site 2. Comparable rates of any/significant NDI were seen across both sites (any NDI: 38% vs 36%; significant NDI: 13% vs 10% for Site 1 and 2, respectively). After adjustments, NDI rates remained similar., Conclusion: PDA management strategies in extremely preterm newborns showed no significant impact on neurodevelopment outcomes at 18-24 months CPA., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Individuals born preterm have reduced aerobic capacity, which could be related to impaired organ development. Their capacity to improve aerobic capacity with exercise training could therefore be limited, but this remains unknown. We aimed to test an exercise intervention to improve cardiorespiratory fitness in adults born preterm., Methods: Twenty-one very preterm and 37 full-term individuals aged 18-33 yr took part in a 14-wk supervised exercise intervention of cardiovascular, resistance, and flexibility training (two group and one individual sessions per week). Adherence and compliance to intervention were recorded. Primary outcome was change in peak oxygen consumption (peak V̇O 2 ) measured before and after the intervention. Within- and between-group differences were estimated using nonparametric tests., Results: Of 219 eligible individuals, 58 were enrolled and 14 participants dropped out over the course of the intervention. Among the 44 who completed the intervention, mean adherence was 82% and 66% for group and individual sessions, respectively. Compliance with training requirement varied between 71% and 100%. There was no difference in adherence between the preterm and full-term groups. Because only one preterm male met the adherence criteria, subsequent analyses were done exclusively on females. Both the term and preterm groups achieved higher peak V̇O 2 after the intervention [term = +4.2 (SD 4.3) mL·min -1 ·kg -1 , P < 0.01; preterm = +4.7 (2.9) mL·min -1 ·kg -1 , P < 0.01]. There was no between-group difference in the response to the intervention ( P = 0.729)., Conclusions: Recruitment and adherence to an exercise intervention are challenging. Results could indicate improvements in cardiorespiratory fitness in young women born preterm after current exercise program. Adaptation of this intervention is needed for wider uptake., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Introduction: Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long-term neurodevelopmental outcomes in very preterm infants (VPIs), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine the long-term neurodevelopmental outcomes of VPIs with late onset sepsis and meningitis, with and without IVH, in Canada., Methods: We conducted a retrospective cohort study of all infants &lt;29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases, from January 1, 2010, to December 31, 2016., Results: Of the 6,322 infants in the cohort, 4,575 had no infection, 1,590 had late onset culture-positive bloodstream infection (CPBSI) only, and 157 had late onset meningitis. There was a significant (p &lt; 0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment, cerebral palsy, and individual Bayley-III scores &lt;85 for cognitive, language, and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis., Conclusion: There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: We identified patient characteristics associated with an increased risk of developing MIS-C., Methods: We conducted a longitudinal cohort study of 1,195,327 patients aged 0-19 years between 2006 and 2021, including the first two waves of the pandemic (February 25-August 22, 2020 and August 23, 2020-March 31, 2021). Exposures included prepandemic morbidity, birth outcomes, and family history of maternal disorders. Outcomes included MIS-C, Kawasaki disease, and other Covid-19 complications during the pandemic. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between patient exposures and these outcomes using log-binomial regression models adjusted for potential confounders., Results: Among 1,195,327 children, 84 developed MIS-C, 107 Kawasaki disease, and 330 other Covid-19 complications during the first year of the pandemic. Prepandemic hospitalizations for metabolic disorders (RR 11.3, 95% CI 5.61-22.6), atopic conditions (RR 3.34, 95% CI 1.60-6.97), and cancer (RR 8.11, 95% CI 1.13-58.3) were strongly associated with the risk of MIS-C, compared with no exposure. These same exposures were also associated with Kawasaki disease and other Covid-19 complications. However, birth characteristics and history of maternal morbidity were not associated with MIS-C development., Conclusions: Children with pre-existing morbidity have a considerably elevated risk of MIS-C., Impact: Morbidities that predispose children to multisystem inflammatory syndrome (MIS-C) are unclear. In this study, prepandemic hospitalizations for metabolic disorders, atopic conditions, and cancer were associated with an elevated risk of MIS-C. Birth characteristics and family history of maternal morbidity were not, however, associated with MIS-C. Pediatric morbidities may play a greater role in MIS-C onset than maternal or perinatal characteristics, and may help clinicians better recognize children at risk for this complication., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background and Objectives: Research on outcomes of prematurity frequently examines neurodevelopment in the toddler years as an end point, but the age range at examination varies. We aimed to evaluate whether the corrected age (CA) at Bayley-III assessment is associated with rates of developmental delay in extremely preterm children., Methods: This retrospective cohort study included children born at <29 weeks' gestation who were admitted in the Canadian Neonatal Network between 2009 and 2017. The primary outcomes were significant developmental delay (Bayley-III score <70 in any domain) and developmental delay (Bayley-III score <85 in any domain). To assess the association between CA at Bayley-III assessment and developmental delay, we compared outcomes between 2 groups of children: those assessed at 18 to 20 months' CA and 21-24 months., Results: Overall, 3944 infants were assessed at 18-20 months' CA and 881 at 21-24 months. Compared with infants assessed at 18-20 months, those assessed at 21-24 months had higher odds of significant development delay (20.0% vs 12.5%; adjusted odds ratio, 1.75; 95% confidence interval [CI], 1.41-2.13) and development delays (48.9% vs 41.7%, adjusted odds ratio 1.33; 95% CI, 1.11-1.52). Bayley-III composite scores were on average 3 to 4 points lower in infants evaluated at 21-24 months' CA (for instance, adjusted mean difference and 95% CI for language: 3.49 [2.33-4.66]). Conversely, rates of cerebral palsy were comparable (4.6% vs 4.7%) between the groups., Conclusions: Bayley-III assessments performed at 21-24 months' CA were more likely to diagnose a significant developmental delay compared with 18- to 20-month assessments in extremely preterm children., (Copyright © 2024 by the American Academy of Pediatrics.)

Aim: To determine the association of successful and unsuccessful operative vaginal delivery attempts with risk of severe neonatal birth injury., Methods: We conducted a population-based observational study of 1 080 503 births between 2006 and 2019 in Quebec, Canada. The main exposure was operative vaginal delivery with forceps or vacuum, elective or emergency cesarean with or without an operative vaginal attempt, and spontaneous delivery. The outcome was severe birth injury, including intracranial hemorrhage, brain and spinal damage, Erb's paralysis and other brachial plexus injuries, epicranial subaponeurotic hemorrhage, skull and long bone fractures, and liver, spleen, and other neonatal body injuries. We determined the association of delivery mode with risk of severe birth injury using adjusted risk ratios (RR) and 95% confidence intervals (CI)., Results: A total of 8194 infants (0.8%) had severe birth injuries. Compared with spontaneous delivery, vacuum (RR 2.98, 95% CI 2.80-3.16) and forceps (RR 3.35, 95% CI 3.07-3.66) were both associated with risk of severe injury. Forceps was associated with intracranial hemorrhage (RR 16.4, 95% CI 10.1-26.6) and brain and spinal damage (RR 13.5, 95% CI 5.72-32.0), while vacuum was associated with epicranial subaponeurotic hemorrhage (RR 27.5, 95% CI 20.8-36.4) and skull fractures (RR 2.04, 95% CI 1.86-2.25). Emergency cesarean after an unsuccessful operative attempt was associated with intracranial and epicranial subaponeurotic hemorrhage, but elective and other emergency cesareans were not associated with severe injury., Conclusions: Operative vaginal delivery and unsuccessful operative attempts that result in an emergency cesarean are associated with elevated risks of severe birth injury., (© 2023 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Introduction: Executive function deficits and adverse psychological outcomes are common in youth with congenital heart disease (CHD) or born preterm. Association white matter bundles play a critical role in higher order cognitive and emotional functions and alterations to their microstructural organization may result in adverse neuropsychological functioning. This study aimed to examine the relationship of myelination and axon density and orientation alterations within association bundles with executive functioning, psychosocial well-being, and resilience in youth with CHD or born preterm., Methods: Youth aged 16 to 26 years born with complex CHD or preterm at ≤33 weeks of gestational age and healthy controls completed a brain MRI and self-report assessments of executive functioning, psychosocial well-being, and resilience. Multicomponent driven equilibrium single-pulse observation of T 1 and T 2 and neurite orientation dispersion and density imaging were used to calculate average myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index values for eight bilateral association bundles. The relationships of bundle-average metrics with neuropsychological outcomes were explored with linear regression and mediation analyses., Results: In the CHD group, lower MWF in several bundles was associated with poorer working memory and behavioral self-monitoring and mediated self-monitoring deficits relative to controls. In the preterm group, lower NDI in several bundles was associated with poorer emotional control and lower MWF in the left superior longitudinal fasciculus III mediated planning/organizing deficits relative to controls. No significant relationships were observed for psychosocial well-being or resilience., Conclusion: The findings of this study suggest that microstructural alterations to association bundles, including lower myelination and axon density, have different relationships with executive functioning in youth with CHD and youth born preterm. Future studies should aim to characterize other neurobiological, social, and environmental influences that may interact with white matter microstructure and neuropsychological functioning in these at-risk individuals., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objectives: Extremely preterm babies have a significant risk of neurodevelopmental impairment (NDI). There has been little investigation regarding the impact of prematurity on families. The objective of this study was to explore parental perspectives regarding the impact of prematurity on themselves/their family., Methods: Over 1 year, parents of children born <29 weeks' gestational age (GA) who were between 18 months old and 7 years old and came for their follow-up visit were invited to participate. They were asked to categorise the impacts of prematurity on their life and their family as positive, negative or both and to describe those impacts in their own words. Thematic analysis was performed by a multidisciplinary group, including parents. Logistic regression was performed to compare parental responses., Results: Among parents (n=248, 98% participation rate), most (74%) reported that their child's prematurity had both positive and negative impacts on their life or their family's life, while 18% reported only positive impacts and 8% only negative impacts. These proportions were not correlated with GA, brain injury, nor level of NDI. The positive impacts reported included: an improved outlook on life, such as gratitude and perspective (48%), stronger family relationships (31%) and the gift of the child (28%). The negative themes were stress and fear (42%), loss of equilibrium due to medical fragility (35%) and concerns about developmental outcomes including the child's future (18%)., Conclusion: Parents report both positive and negative impacts after an extremely preterm birth, independent of disability. These balanced perspectives should be included in neonatal research, clinical care and provider education., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU)., Methods: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression., Results: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU., Conclusions: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages., Impact: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

This study aims to compare cardiopulmonary response to aerobic exercise between young adults born very preterm, including a subgroup with bronchopulmonary dysplasia (BPD), and term controls.Seventy-one adults (18-29 years) born <30 weeks' gestational age (24 with BPD) and 73 term controls were recruited. Assessment included cardiopulmonary exercise testing with impedance cardiography. We compared group differences in peak O 2 consumption (peak VO 2 ) and in ventilatory and cardiovascular responses to exercise using linear regression analyses.Preterm participants had reduced peak VO 2 (mean difference -2.7; 95% CI -5.3, -0.1 mL·kg -1 lean body mass·min -1 ) versus controls. Those with BPD achieved lower peak work-rate compared to term controls (-21; 95% CI -38, -5 watts). There was no difference across groups in breathing reserve, ventilatory efficiency, peak heart rate and cardiac output. VO 2 to work-rate relationship (ΔVO 2 /ΔWR) was reduced in preterm versus term. Peak systolic blood pressure and circulatory power (systolic blood pressure*VO 2 ) were also lower in BPD versus term controls. In the preterm group, longer NICU stay and lower peak cardiac output were associated with lower peak VO 2 Results suggest limitations with peripheral O 2 uptake in the muscle with reduced ΔVO 2 /ΔWR and peak circulatory power, but normal cardiac output. Investigations into skeletal muscle perfusion and O 2 use during exercise are warranted to better understand mechanisms of exercise limitation., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction : Support groups in neonatal intensive care units (NICUs) are beneficial to parents. The usefulness of prenatal support groups for prospective parents who will have a newborn requiring admission to the NICU has never been investigated. Methods : We assessed the needs of NICU parents regarding topics they would have wished to discuss prenatally and developed the content of a prenatal support workshop. A standardized survey prospectively evaluated the perspectives of pregnant women admitted to a high-risk pregnancy unit who participated in the resulting workshops. Results : During needs assessment, 295 parents invoked themes they would have wished to discuss antenatally: parental guilt, future parental role, normalizing their experience/emotions, coping with many losses, adapting to their new reality, control and trust, information about the NICU, technology around the baby, common neonatal interventions, the NICU clinical team, and the role of parents in the team. These findings were used to develop the workshop, including a moderator checklist and a visual presentation. Practical aspects of the meetings were tested/finalized during a pre-pilot phase. Among 21 pregnant women who answered the survey (average gestational age 29.3 weeks), all agreed that the workshop was useful, that it made them feel less lonely (95%), that exchanges with other women were beneficial (95%) and gave them a certain amount of control over their situation (89%). All answers to open-ended questions were positive. Conclusion : Prenatal educational/support workshops provide a unique and useful means to support future NICU parents. Future investigations will explore whether these prenatal interventions improve clinical outcomes.

Introduction: Although relevant for precision pharmacovigilance, there are conflicting data on whether former preterm birth is associated with QT c-Bazett prolongation in later life., Methods: To explore QT c-Bazett interval differences between former preterm and/or extremely low birth weight (ELBW) cases and term-born controls in adolescence and young adulthood, we analyzed pooled individual data after a structured search on published cohorts. To test the absence of a QT c-Bazett difference, a non-inferiority approach was applied (one-sided, upper limit of the 95% confidence interval [CI] mean QT c-Bazett difference, 5 and 10 ms). We also investigated the impact of characteristics, either perinatal or at assessment, on QT c-Bazett in the full dataset (cases and controls). Data were reported as median and range., Results: The pooled dataset contained 164 former preterm and/or ELBW (cases) and 140 controls born full-term from three studies. The median QT c-Bazett intervals were 409 (335-490) and 410 (318-480) ms in cases and controls. The mean QT c-Bazett difference was 1 ms, with an upper 95% CI of 6 ms (p > 0.05 and p < 0.01 for 5 and 10 ms, respectively). In the full dataset, females had a significantly longer QT c-Bazett than males (415 vs. 401 ms; p < 0.0001)., Conclusions: QT c-Bazett intervals are not significantly different between former preterm and/or ELBW cases and term-born controls, and we rejected a potential prolongation > 10 ms in cases. When prescribing QTc-prolonging drugs, pharmacovigilance practices in this subpopulation should be similar to the general public (NCT05243537)., (© 2023. The Author(s).)

Background: Maternal suicide attempts are associated with adverse psychosocial outcomes in children, but the association with chronic morbidity is poorly understood. We examined the relationship between maternal suicide attempt and risk of hospitalization for potentially preventable conditions in offspring., Methods: We analyzed a longitudinal cohort of 1 032 210 children born in Quebec, Canada between 2006 and 2019. The main exposure measure was maternal suicide attempt before or during pregnancy. Outcomes included child hospitalizations for potentially preventable conditions, including infectious diseases, dental caries, atopy, and injury up to 14 years after birth. We used adjusted Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of maternal suicide attempt with risk of hospitalization for these outcomes., Results: Compared with no suicide attempt, children whose mothers attempted suicide had an increased risk of hospitalization for infectious diseases (HR 1.11, 95% CI 1.06-1.16), dental caries (HR 1.31, 95% CI 1.15-1.48), and injury (HR 1.16, 95% CI 1.03-1.31). Risk of hospitalization for any of these outcomes was greater if mothers attempted suicide by hanging (HR 1.46, 95% CI 1.22-1.75), had their first attempt between the age of 25 and 34 years (HR 1.27, 95% CI 1.13-1.42), and had 3 or more attempts (HR 1.56, 95% CI 1.27-1.91). Maternal suicide attempts were more strongly associated with child hospitalization before 10 years of age., Conclusions: Children whose mothers have a history of suicide attempt have an elevated risk of hospitalization for potentially preventable conditions.

Background: We studied the effect of the Covid-19 pandemic on child eating disorder hospitalizations in Quebec, Canada. Quebec had one of the strictest lockdown measures targeting young people in North America., Methods: We analyzed eating disorder hospitalizations in children aged 10-19 years before and during the pandemic. We used interrupted time series regression to assess trends in the monthly number of hospitalizations for anorexia nervosa, bulimia nervosa, and other eating disorders before the pandemic (April 2006 to February 2020), and during the first (March to August 2020) and second waves (September 2020 to March 2021). We determined the types of eating disorders requiring hospital treatment and identified the age, sex and socioeconomic subgroups that were most affected., Results: Hospitalization rates for eating disorders increased during the first (6.5 per 10,000) and second waves (12.8 per 10,000) compared with the period before the pandemic (5.8 per 10,000). The increase occurred for anorexia nervosa as well as other types of eating disorders. The number of girls and boys aged 10-14 years admitted for eating disorders increased during wave 1. Wave 2 triggered an increase in eating disorder admissions among girls aged 15-19 years. Hospitalization rates increased earlier for advantaged than disadvantaged youth., Conclusions: The Covid-19 pandemic affected hospitalizations for anorexia nervosa as well as other eating disorders, beginning with girls aged 10-14 years during wave 1, followed by girls aged 15-19 years during wave 2. Boys aged 10-14 years were also affected, as well as both advantaged and disadvantaged youth., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Aim: The aim of the study was to explore how young adults thought that being born preterm had affected their lives., Methods: Adult participants of a research cohort were questioned about their perspectives. Answers were analysed using mixed methods., Results: Forty-five participants evaluated their health at median score of 8/10. When asked about the meaning of being born preterm, 65% had positive self-centred answers, invoking two main themes: being stronger/'a fighter'/more resilient and being a survivor/chosen; 42% also reported negative themes, such as having health problems and a difficult start. All heard about their prematurity from their parents, 55% with positive child-centred or healthcare system-centred themes, 19% with neutral themes; 35% also heard negative parent-centred themes (tragic experience, guilt, mother's health). When asked which words were associated with prematurity, participants mainly chose positive words for themselves and their family, but more negative words for how the media and society depicted prematurity. Answers were not correlated with adverse objective health measures., Conclusion: Participants evaluated their health in a balanced fashion. Preterm-born adults often feel that they have experienced positive transformations as a result of their traumatic start. They often have feelings of gratitude and strength, independent of health problems., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Purpose: To determine if suicide attempts increased during the first year of the pandemic among young adolescents in Quebec, Canada., Methods: We analyzed children aged 10-14 years who were hospitalized for a suicide attempt between January 2000 and March 2021. We calculated age-specific and sex-specific suicide attempt rates and the proportion of hospitalizations for suicide attempts before and during the pandemic and compared rates with patients aged 15-19 years. We used interrupted time series regression to measure changes in rates during the first (March 2020 to August 2020) and second (September 2020 to March 2021) waves and difference-in-difference analysis to determine if the pandemic had a greater impact on girls than boys., Results: Suicide attempt rates decreased for children aged 10-14 years during the first wave. However, rates increased sharply during the second wave for girls, without changing for boys. Girls aged 10-14 years had an excess of 5.1 suicide attempts per 10,000 at the start of wave 2, with rates continuing to increase by 0.6 per 10,000 every month thereafter. Compared with the prepandemic period, the increase in the proportion of girls aged 10-14 years hospitalized for a suicide attempt was 2.2% greater than that of boys during wave 2. The pattern seen in girls aged 10-14 years was not present in girls aged 15-19 years., Discussion: Hospitalizations for suicide attempts among girls aged 10-14 years increased considerably during the second wave of the pandemic, compared with boys and older girls. Young adolescent girls may benefit from screening and targeted interventions to address suicidal behavior., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Cycling increased in popularity during the COVID-19 pandemic, but the impact on cycling injuries is not known. We examined the effect of lockdowns on cycling injury hospitalizations., Methods: We identified hospitalizations for cycling injuries in Quebec, Canada, between April 2006 and March 2021. We used rate ratios (RR) and 95% confidence intervals (CI) to compare hospitalization rates by type of cycling injury and anatomical site during two waves of the pandemic. We performed interrupted time series regression to assess the effect of lockdowns on monthly cycling injury hospitalization rates, according to age, sex and other characteristics., Results: There were 2020 hospitalizations for cycling injuries between March 2020 and March 2021, including 617 during the first lockdown and 67 during the second lockdown. Compared with the period before the pandemic, risk of cycling-related injuries during the first lockdown increased the most for fractures (RR = 1.44; 95% CI: 1.26- 1.64) and head and neck injuries (RR = 1.59; 95% CI: 1.19-2.12). Cycling injury hospitalization rates increased significantly among adults, adolescents and individuals from socioeconomically advantaged neighbourhoods or those with low concentrations of racialized people every month of the first lockdown. The second lockdown was not associated with cycling injuries., Conclusion: The first lockdown triggered a sharp increase in cycling injury hospitalizations, especially among adults, adolescents and individuals from socioeconomically advantaged and less racialized neighbourhoods., Competing Interests: The authors have no financial relationships relevant to this article and no conflicts of interest to disclose.

Objectives: To explore decisional regret of parents of babies born extremely preterm and analyze neonatal, pediatric, and parental factors associated with regret., Study Design: Parents of infants born <29 weeks of gestational age, aged between 18 months and 7 years, attending neonatal follow-up were enrolled. Hospital records were reviewed to examine morbidities and conversations with parents about levels of care. Parents were asked the following question: "Knowing what you know now, is there anything you would have done differently?" Mixed methods were used to analyze responses., Results: In total, 248 parents (98% participation) answered, and 54% reported they did not have regret. Of those who reported regret (n = 113), 3 themes were most frequently invoked: 35% experienced guilt, thinking they were responsible for the preterm birth; 28% experienced regret about self-care decisions; and 20% regretted decisions related to their parental role, generally wishing they knew sooner how to get involved. None reported regret about life-and-death decisions made at birth or in the neonatal intensive care unit. Impairment at follow-up, gestational age, and decisions about levels/reorientation of care were not associated with regret. More mothers reported feeling guilt about the preterm birth (compared with fathers); parents of children with severe lesions on ultrasonography of the head were less likely to report regret., Conclusions: Approximately one-half of the parents of infants born extremely preterm had regrets regarding their neonatal intensive care unit stay. Causes of regret and guilt should be addressed and minimized., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The possibility that child maltreatment was misclassified as unintentional injury during the COVID-19 pandemic has not been evaluated., Objective: We assessed if child maltreatment hospitalizations changed during the pandemic, and if the change was accompanied by an increase in unintentional injuries., Participants and Setting: This study included children aged 0-4 years who were admitted for maltreatment or unintentional injuries between April 2006 and March 2021 in hospitals of Quebec, Canada., Methods: We used interrupted time series regression to estimate the effect of the pandemic on hospitalization rates for maltreatment, compared with unintentional transport accidents, falls, and mechanical force injuries. We assessed if the change in maltreatment hospitalization was accompanied by an increase in specific types of unintentional injury., Results: Hospitalizations for child maltreatment decreased from 16.3 per 100,000 (95 % CI 9.1-23.4) the year before the pandemic to 13.2 per 100,000 (95 % CI 6.7-19.7) during the first lockdown. Hospitalizations for most types of unintentional injury also decreased, but injuries due to falls involving another person increased from 9.0 to 16.5 per 100,000. Hospitalization rates for maltreatment and unintentional injury remained low during the second lockdown, but mechanical force injuries involving another person increased from 3.8 to 8.1 per 100,000., Conclusions: Hospitalizations for child maltreatment may have been misclassified as unintentional injuries involving another person during the pandemic. Children admitted for these types of unintentional injuries may benefit from closer assessment to rule out maltreatment., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Neurodevelopmental challenges in children born very preterm are common and not improving. This study tested the feasibility of using Evidence-based Practice to Improve Quality (EPIQ), a proven quality improvement technique that incorporates scientific evidence to target improving language abilities in very preterm populations in 10 Canadian neonatal follow-up programs. Feasibility was defined as at least 70% of sites completing four intervention cycles and 75% of cycles meeting targeted aims. Systematic reviews were reviewed and performed, an online quality improvement educational tool was developed, multidisciplinary teams that included parents were created and trained, and sites provided virtual support to implement and audit locally at least four intervention cycles of approximately 6 months in duration. Eight of ten sites implemented at least four intervention cycles. Of the 48 cycles completed, audits showed 41 (85%) met their aim. Though COVID-19 was a barrier, parent involvement, champions, and institutional support facilitated success. EPIQ is a feasible quality improvement methodology to implement family-integrated evidence-informed interventions to support language interventions in neonatal follow-up programs. Further studies are required to identify potential benefits of service outcomes, patients, and families and to evaluate sustainability.

Children born very preterm are at risk of severe neurodevelopmental impairment, a composite endpoint that includes cerebral palsy, developmental delay, and hearing and visual impairment defined by medical professionals. We aimed to describe preterm birth stakeholders' perspectives on this classification. Ten clinical scenarios describing 18-month-old children with different components of severe neurodevelopmental impairment and one scenario of a typically developing child (control) were distributed to parents and stakeholders using a snowball sampling technique. For each scenario, participants rated health on a scale from 0 to 10 and whether the scenario represented a severe condition. Results were analyzed descriptively and mean differences from the control scenario were compared using a linear mixed-effects model. Stakeholders (number = 827) completed 4553 scenarios. Median health scores for each scenario varied from 6 to 10. The rating for the cerebral palsy and language delay scenario was significantly lower (mean difference -4.3; 95% confidence interval: -4.4, -4.1) than the control. The proportion of respondents rating a scenario as "severe" ranged from 5% for cognitive delay to 55% for cerebral palsy and language delay. Most participants disagreed with the rating used in research to describe severe neurodevelopmental impairment in preterm children. The term should be redefined to align with stakeholder perceptions.

Introduction: Alterations to white matter microstructure as detected by diffusion tensor imaging have been documented in both individuals born with congenital heart disease (CHD) and individuals born preterm. However, it remains unclear if these disturbances are the consequence of similar underlying microstructural disruptions. This study used multicomponent driven equilibrium single pulse observation of T 1 and T 2 (mcDESPOT) and neurite orientation dispersion and density imaging (NODDI) to characterize and compare alterations to three specific microstructural elements of white matter - myelination, axon density, and axon orientation - in youth born with CHD or born preterm., Methods: Participants aged 16 to 26 years with operated CHD or born ≤33 weeks gestational age and a group of healthy peers of the same age underwent a brain MRI including mcDESPOT and high angular resolution diffusion imaging acquisitions. Using tractometry, average values of myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index (ODI) were first calculated and compared between groups for 30 white matter bundles. Afterwards, bundle profiling was performed to further characterize the topology of the detected microstructural alterations., Results: The CHD and preterm groups both presented with widespread bundles and bundle segments with lower MWF, accompanied by some occurrences of lower NDI, relative to controls. While there were no differences in ODI between the CHD and control groups, the preterm group presented with both higher and lower ODI compared to the control group and lower ODI compared to the CHD group., Discussion: While youth born with CHD or born preterm both presented with apparent deficits in white matter myelination and axon density, youth born preterm presented with a unique profile of altered axonal organization. Future longitudinal studies should aim to better understand the emergence of these common and distinct microstructural alterations, which could orient the development of novel therapeutic approaches., Competing Interests: GG is an employee of Philips Healthcare Canada. MD is an employee, co-founder, and co-owner of Imeka Solutions Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Easson, Khairy, Rohlicek, Saint-Martin, Gilbert, Nguyen, Luu, Couture, Nuyt, Wintermark, Deoni, Descoteaux and Brossard-Racine.)

Background: Mild traumatic brain injury (mTBI) sustained in early childhood affects the brain at a peak developmental period and may disrupt sensitive stages of skill acquisition, thereby compromising child functioning. However, due to the challenges of collecting non-sedated neuroimaging data in young children, the consequences of mTBI on young children's brains have not been systematically studied. In typically developing preschool children (of age 3-5years), a brief behavioral-play familiarization provides an effective alternative to sedation for acquiring awake magnetic resonance imaging (MRI) in a time- and resource-efficient manner. To date, no study has applied such an approach for acquiring non-sedated MRI in preschool children with mTBI who may present with additional MRI acquisition challenges such as agitation or anxiety., Objective: The present study aimed to compare the effectiveness of a brief behavioral-play familiarization for acquiring non-sedated MRI for research purposes between young children with and without mTBI, and to identify factors associated with successful MRI acquisition., Materials and Methods: Preschool children with mTBI (n=13) and typically developing children (n=24) underwent a 15-minutes behavioral-play MRI familiarization followed by a 35-minutes non-sedated MRI protocol. Success rate was compared between groups, MRI quality was assessed quantitatively, and factors predicting success were documented., Results: Among the 37 participants, 15 typically developing children (63%) and 10 mTBI (77%) reached the MRI acquisition success criteria (i.e., completing the two first sequences). The success rate was not significantly different between groups (p=.48; 95% CI [-0.36 14.08]; Cramer's V=.15). The images acquired were of high-quality in 100% (for both groups) of the structural images, and 60% (for both groups) of the diffusion images. Factors associated with success included older child age (Β=0.73, p=.007, exp(B)=3.11, 95% CI [1.36 7.08]) and fewer parental concerns (Β=-1.56, p=.02, exp(Β)=0.21, 95% CI [0.05 0.82]) about the MRI procedure., Conclusion: Using brief behavioral-play familiarization allows acquisition of high-quality non-sedated MRI in young children with mTBI with success rates comparable to those of non-injured peers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To describe pulmonary important outcomes (PIO) reported by parents of children born extremely preterm., Methods: Over 1-year, all parents of children aged 18 months-7-years born <29 weeks' GA were asked regarding their perspectives. The proportion of parents who described PIO and the themes they invoked were examined. Results were analysed using mixed methods., Results: Among parental responses (n = 285, 98% participation rate), 44% spoke about PIO, invoking 24 themes pertaining to NICU hospitalisation and/or long-term respiratory health. Some themes had an impact primarily on the child (e.g. exercise limitation), while the majority had an impact on the whole family (e.g. hospital readmissions). None mentioned oxygen at 36 weeks nor bronchopulmonary dysplasia (BPD). The proportion of responses invoking PIO were statistically similar between parents of children with and without BPD, born before or after 25 weeks or with birthweight < or ≥750 g. PIO were more likely to be mentioned in males and among those readmitted for respiratory problems., Conclusion: Parents describe many PIO, most related to the functional impact of lung disease on their child (and family), rather than the diagnosis of BPD itself. Most of these PIO are not primary outcomes in large neonatal trials nor collected in neonatal databases., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Introduction: Children with a history of bronchopulmonary dysplasia (BPD) may have lower physical activity levels, but evidence to date is mixed. This study compared physical activity levels between children born extremely preterm with and without history of BPD, and examined their associations with pulmonary magnetic resonance imaging (MRI) and pulmonary function test (PFT) indices., Methods: This multicentre cross-sectional study included children aged 7-9 years born extremely preterm, with and without BPD. Children wore a pedometer for 1 week, then completed the Physical Activity Questionnaire (PAQ), pulmonary MRI, and PFT. Spearman correlations and multivariable linear regression modeling were performed., Results: Of 45 children, 28 had a history of moderate-severe BPD. There were no differences in any physical activity outcomes by BPD status. Higher average daily step count and higher average daily moderate-to-vigorous physical activity (MVPA) were each correlated with greater forced vital capacity (r = 0.41 and 0.58), greater MRI lung proton density at full expiration (r = 0.42 and 0.49), and lower lung clearance index (r = -0.50 and -0.41). After adjusting for MRI total proton density and BPD status, a 5% increase in forced expiratory volume at 1 s was associated with 738 (95% CI: 208, 1268) more steps per day and 0.1 (0.0, 0.2) more hours of MVPA, respectively., Conclusion: School-aged children born extremely preterm have similar physical activity levels to their peers, regardless of history of BPD. MRI and PFT measures suggestive of gas trapping and/or airflow obstruction are associated with lower physical activity levels., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Objective: To examine associations between weight and head circumference (HC) changes and neurodevelopment in preterm infants., Study Design: This retrospective cohort study of Canadian Neonatal Network and Canadian Neonatal Follow-Up Network sites included preterm infants born 2010-2018. Logistic regression and model diagnostics evaluated relationships between changes in z score and velocity of weight and HC from birth to discharge from a tertiary neonatal intensive care unit, discharge to 18-24 months corrected age (CA), and birth to 18-24 months CA and significant cognitive/motor impairment at 18-24 months CA classified using a Bayley Scales of Infant and Toddler Development-Third Edition cognitive or motor composite score <70., Results: In total, 4530 infants (53.0% male) with a mean (SD) gestational age of 26.3 (1.4) weeks and birth weight of 920 (227) g were included. Weight and HC changes were associated with lower odds of significant cognitive/motor impairment including an OR of 0.87 (95% CI: 0.83, 0.91; P < .001) for a 1-g/d increase in weight from discharge to 18-24 months CA and 0.81 (95% CI: 0.75, 0.88; P < .001) for a 1-unit increase in HC z score from birth to 18-24 months CA. Associations were not statistically significant in morbidity-free neonates. Weight and HC gains poorly discriminated between infants with and without significant cognitive/motor impairment (areas under the receiver operating characteristic curve of <0.64). No growth measure had a clinically useful balance of sensitivity and specificity., Conclusions: Weight and HC changes were associated with significant cognitive/motor impairment but had poor discriminatory capability. Neonatal morbidities may make a larger contribution than postnatal growth to neurodevelopment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Invasive fungal infection (IFI) is associated with significant mortality and morbidity among preterm infants but there has been no population-based study of long-term neurodevelopmental outcomes. The objective of this study was to examine population-based incidence trends as well as mortality, short term in-hospital morbidity and long-term neurodevelopmental outcomes among preterm infants with IFI, non-fungal infections (NFI) and no infections in Canada., Methods: We conducted a retrospective cohort study of 8,408 infants born at <29 weeks gestational age (GA), admitted to Canadian Neonatal Network neonatal intensive care units (NICU) from April 2009 to December 2017, and followed up at 18-30 months corrected age (CA) in Canadian Neonatal Follow-Up Network clinics. We compared mortality, long term neurodevelopmental outcomes and short term in-hospital morbidity among 3 groups of infants (IFI, NFI, and no infections)., Results: The incidence of IFI was 1.3%, non-IFI 26.9% and no infections 71.7%. IFI incidence varied between 0.93% and 1.94% across the study period with no significant trend over time. Infants of higher gestational age were significantly ( p  < 0.01) less likely to have IFI. Among infants with IFI, NFI and no infections, the incidence of the significant neurodevelopmental impairment (sNDI) was 44.26%, 21.63% and 14.84% respectively, while mortality was 50%, 25.35% and 22.25% respectively. Even after risk adjustment for confounders (GA, Score for Neonatal Acute Physiology Version II, ruptured membranes >24 h, maternal antibiotic treatment, antenatal steroid use, cesarean section), infants with IFI had significantly higher odds of sNDI than NFI (aOR: 2.19; 95% CI: 1.23, 3.91) or no infections (aOR: 2.97; 95% CI: 1.55, 5.71), and higher odds of mortality than NFI (aOR: 1.55; 95% CI: 1.07, 2.26) or no infections (aOR: 1.45; 95% CI: 0.97, 2.17)., Conclusions: Preterm infants with invasive fungal infections have significantly higher incidence of mortality and adverse neurodevelopmental outcomes than those with non-invasive fungal infections and no infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhou, Kelly, Luu, Ye, Ting, Shah and Lee.)

Introduction: Therapeutic hypothermia (TH) became the standard of care treatment for neonates with moderate and severe neonatal encephalopathy (NE) in most industrialized countries about 10 years ago. Although TH is effective in reducing mortality and the incidence of severe developmental disabilities, the recent literature converges in reporting frequent cognitive and behavioural difficulties at school entry in children with NE-TH. Although these challenges are deemed minor compared with cerebral palsy and intellectual disability, their impacts on a child's self-determination and family's well-being are quite significant. Therefore, the nature and extent of these difficulties need to be comprehensively described so that appropriate care can be offered., Methods and Analysis: The current study will be the largest follow-up study of neonates with NE treated with TH to characterize their developmental outcomes and associated brain structural profiles at 9 years of age. Specifically, we will compare executive function, attention, social cognition, behaviour, anxiety, self-esteem, peer problems, brain volume, cortical features, white matter microstructure and myelination between children with NE-TH and matched peers without NE. Associations of perinatal risk factors and structural brain integrity with cognitive, behavioural and psycho-emotional deficits will be evaluated to inform about the potential aggravating and protective factors associated with function., Ethics and Dissemination: This study is supported by the Canadian Institute of Health Research (202203PJT-480065-CHI-CFAC-168509), and received approval from the Pediatric Ethical Review Board of the McGill University Health Center (MP-37-2023-9320). The study findings will be disseminated in scientific journals and conferences and presented to parental associations and healthcare providers to inform best practices., Trial Registration Number: NCT05756296., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Infants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA)., Methods: Preterm infants ( N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO 2 ). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO 2 i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA., Results: Steeper increases in CBF i ( p < 0.0001) and CMRO 2 i ( p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO 2 i from birth to TEA were not associated with neurological examination at TEA., Conclusion: In this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO 2 i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Côté-Corriveau, Simard, Beaulieu, Chowdhury, Gagnon, Gagnon, Ledjiar, Bernard, Nuyt, Dehaes and Luu.)

Background: We identified maternal and neonatal birth characteristics that were associated with organ or tissue transplants during childhood., Methods: We designed a retrospective cohort study of the population of children born between 2006 and 2019 in Quebec, Canada. The exposure included birth complications such as congenital anomaly, neonatal blood transfusion, and oligohydramnios. The main outcome measure was organ or tissue transplantation before 14 y of age. We categorized transplants according to type (major organs versus superficial tissues). To determine the association of birth characteristics with risk of pediatric transplant, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards models adjusted for potential confounders., Results: The cohort comprised 1 038 375 children with 7 712 678 person-years of follow-up, including 436 children who had transplants before 14 y of age. Birth complications were predominantly associated with major organ transplants. Congenital anomaly was associated with heart or lung (HR, 10.41; 95% CI, 5.33-20.33) and kidney transplants (HR, 13.69; 95% CI, 7.48-25.06), compared with no anomaly. Neonatal blood transfusion was associated with all major organ transplants, compared with no transfusion. Maternal complications were not as strongly associated with the risk of childhood transplant, although oligohydramnios was associated with 16.84 times (95% CI, 8.09-35.02) the risk of kidney transplant, compared with no oligohydramnios., Conclusions: Adverse birth outcomes such as congenital anomaly, neonatal blood transfusion, and maternal oligohydramnios are associated with a greater risk of transplantation before 14 y of age. Maternal and neonatal birth outcomes may be useful predictors of transplantation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To describe parental perspective on health and developmental outcomes of their preterm child in relation to level of neurodevelopmental impairment (NDI)., Methods: A parental survey about their children aged 15-36 months corrected age born ˂29 weeks' gestation investigated parental concerns and positive attributes. Parental responses in relation to their child's level of NDI were examined using Kruskal-Wallis and chi-square for trend tests., Results: One hundred ninety-nine parental responses were obtained for 163 children, including 44% with NDI. Vast majority of parents reported their children were developing well with good physical health. All parents, irrespective of NDI, reported their children were happy and had a positive personality. Appreciation of social interactions was higher for parents of children without versus with NDI (96% vs. 87%, p = 0.039). Parents of children with NDI were more likely to express concerns than those without NDI. Overall, development was the most common area of concern (45%), followed by the child's future (40%) and physical health (35%)., Conclusion: Parents of preterm children report many positive points and concerns, some of which are not examined in neonatal follow-up data. These parental perspectives could be used to inform parents of preterm infants, both antenatally and in the neonatal unit., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aims: We assessed the impact of Covid-19 on gestational diabetes rates in Quebec, the pandemic epicenter of Canada., Methods: We conducted a population-based study of 569,686 deliveries in Quebec between 2014 and 2021. We measured gestational diabetes rates in wave 1 (March 1, 2020-August 22, 2020) and wave 2 (August 23, 2020-March 31, 2021), compared with the prepandemic period. We used interrupted time series regression to assess changes in gestational diabetes rates during each wave, and log-binomial regression models to estimate adjusted risk ratios (RR) and 95% confidence intervals (CI) for the association of the pandemic with gestational diabetes. We identified the types of patients that contributed to the change in gestational diabetes rates using Kitagawa's decomposition., Results: Gestational diabetes rates were higher during the first (13.2 per 100 deliveries) and second waves (14.3 per 100 deliveries) than during the prepandemic period (12.4 per 100 deliveries). Risk of gestational diabetes increased both in wave 1 (RR 1.05, 95% CI 1.02-1.09) and wave 2 (RR 1.14, 95% CI 1.10-1.18), compared with the prepandemic period. However, most of the increase in gestational diabetes rates was driven by low-risk women without Covid-19 infections who were socioeconomically advantaged, had no comorbidity, and were 25-34 years of age., Conclusions: Gestational diabetes rates increased during the pandemic, mainly among women traditionally at low risk of hyperglycemia who did not have Covid-19 infections. Sudden widespread changes in screening or lifestyle can have a large impact on gestational diabetes rates in a population., (© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

This study aimed to evaluate symptoms of sleep-disordered breathing (SDB) among children born extremely preterm, with and without a history of bronchopulmonary dysplasia (BPD), including associations between sleep and respiratory symptoms, physical activity, pulmonary function, and pulmonary magnetic resonance imaging (MRI). This multi-center cross-sectional study enrolled children aged 7-9 years born extremely preterm with and without BPD. Participants completed the Pediatric Sleep Questionnaire (PSQ), the modified Epworth sleepiness scale, a respiratory symptom questionnaire, pedometer measurements, pulmonary function testing, and pulmonary MRI. Spearman's correlations and univariate and multivariable linear regression modelling were performed. Twenty-eight of 45 children included had a history of moderate-to-severe BPD. The prevalence of sleep-related symptoms was low, with the exception of hyperactivity and inattention. There were no differences in mean (SD) scores on sleep questionnaires in children with and without BPD (PSQ: 0.21 (0.13) vs 0.16 (0.14), p = 0.3; modified Epworth: 2.4 (2.4) vs 1.8 (2.8), p = 0.4). Multiple regression analyses examining difference in sleep scores between groups, adjusting for gestational age and intraventricular hemorrhage, found no statistical difference (p > 0.05). Greater daytime sleepiness was moderately correlated with FEV1%-predicted (r =  - 0.52); no other moderate-strong associations were identified.  Conclusions: There was no evidence of clinically important differences in sleep symptoms between children with and without BPD, suggesting that sleep symptoms may be related to prematurity-related factors other than a BPD diagnosis, including airflow limitation. Further research is necessary to explore the relationship between sleep symptoms, airway obstruction, and neurobehavioral symptoms among premature-born children.  Trial registration: NCT02921308. Date of registration: October 3, 2016. What is Known: • Presence of bronchopulmonary dysplasia (BPD) may further contribute to the development of SDB, though its impact is not well-studied. • Premature-born children have a greater risk of lung structural and functional differences, including sleep-disordered breathing (SDB). What is New: • There was no difference in sleep symptoms between children with and without BPD, suggesting that sleep symptoms are related to other prematurity-related factors, such as airflow limitation. • Greater daytime sleepiness was correlated with lower FEV1 in our population, which reflects greater airflow limitation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Preterm birth may affect maternal mental health, yet most studies focus on postpartum mental disorders only. We explored the relationship between preterm delivery and the long-term risk of maternal hospitalization for mental illness after pregnancy., Methods: We performed a longitudinal cohort study of 1,381,300 women who delivered between 1989 and 2021 in Quebec, Canada, and had no prior history of mental illness. The exposure was preterm birth, including extreme (<28 weeks), very (28-31 weeks), and moderate to late (32-36 weeks). The outcome was subsequent maternal hospitalization for depression, bipolar, psychotic, stress and anxiety, personality disorders, and self-harm up to 32 years later. We used adjusted Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between preterm birth and mental illness hospitalization., Results: Compared with term, women who delivered preterm had a higher rate of mental illness hospitalization (3.81 vs. 3.01 per 1000 person-years). Preterm birth was associated with any mental illness (HR 1.38, 95% CI 1.35-1.41), including depression (HR 1.37, 95% CI 1.32-1.41), psychotic disorders (HR 1.35, 95% CI 1.25-1.44), and stress and anxiety disorders (HR 1.42, 95% CI 1.38-1.46). Delivery at any preterm gestational age was associated with the risk of mental hospitalization, but risks were greatest around 34 weeks of gestation. Preterm birth was strongly associated with mental illness hospitalization within 2 years of pregnancy, although associations persisted throughout follow-up., Conclusions: Women who deliver preterm may be at risk of mental disorders in the short and long term., (© 2022. The Author(s).)

Objective: To determine the association between postnatal age (PNA) at first administration of systemic postnatal steroids (sPNS) for bronchopulmonary dysplasia (BPD) and mortality or significant neurodevelopmental impairment (sNDI) at 18−24 months corrected age (CA) in infants < 29 weeks’ gestation. Methods: Data from the Canadian Neonatal Network and Canadian Neonatal Follow-up Network databases were used to conduct this retrospective cohort study. Infants exposed to sPNS for BPD after the 1st week of age were included and categorized into 8 groups based on the postnatal week of the exposure. The primary outcome was a composite of mortality or sNDI. A multivariable logistic regression model adjusting for potential confounders was used to determine the association between the sPNS and ND outcomes. Results: Of the 10,448 eligible infants, follow-up data were available for 6200 (59.3%) infants. The proportion of infants at first sPNS administration was: 8%, 17.5%, 23.1%, 18.7%, 12.6%, 8.3%, 5.8%, and 6% in the 2nd, 3rd, 4th, 5th, 6th, 7th, 8−9th, and ≥10th week of PNA respectively. No significant association between the timing of sPNS administration and the composite outcome of mortality or sNDI was observed. The odds of sNDI and Bayley-III motor composite < 70 increased by 1.5% (95% CI 0.4, 2.9%) and 2.6% (95% CI 0.9, 4.4%), respectively, with each one-week delay in the age of initiation of sPNS. Conclusions: No significant association was observed between the composite outcome of mortality or sNDI and PNA of sPNS. Among survivors, each week’s delay in initiation of sPNS may increase the odds of sNDI and motor delay.

Background: Sodium fluctuations in very preterm neonates and their neurodevelopmental consequences are not well described., Methods: We assessed the changes in plasma sodium and glucose in the first days of life in very preterm neonates and studied the association of glucose-corrected plasma sodium fluctuations on neurodevelopmental outcomes. We included 147 consecutive neonates born before 29 weeks of gestation in our center and retrospectively obtained plasma sodium, glucose, and glucose-corrected sodium levels. Neurodevelopmental assessment was obtained from the Canadian Neonatal Follow-Up Network., Results: Mean ± standard deviation of plasma sodium changes within the first 10 days of life were 16.2 ± 6.0, 14.8 ± 5.3, and 11.1 ± 5.2 mmol/l in neonates born ≤25, 25-26, and 26-27 weeks of gestation, respectively (p < 0.001). Non-steroidal anti-inflammatory drug administration was associated with larger plasma sodium fluctuation. Eighty-six percent had a known neurological status at 18 months. Higher fluctuations in glucose-corrected plasma sodium were associated with death or neurodevelopmental impairment at 18 months corrected age (B = 3.19, 95% CI [1.24, 5.14]), and this association remained after adjustment for gestational age (B = 2.1, 95% CI [0.16, 4.04])., Conclusions: Neonates born very preterm show fluctuations in glucose-corrected plasma sodium during the first days of life, which may increase the risk of death or developmental impairment., Impact: Risk factors and neurodevelopmental consequences of plasma sodium changes in early neonatal life of preterm infants are not well characterized. This study shows for the first time that glucose-corrected plasma sodium fluctuations within the first days of life are more severe in preterm infants receiving non-steroidal anti-inflammatory drugs (NSAIDs) and are associated with death or neurodevelopmental impairment at 18 months corrected age. Large plasma sodium and glucose fluctuations should be expected more often in preterm infants receiving NSAIDs and should be avoided., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Introduction: Brief Resolved Unexplained Events (BRUEs) are a common presentation among infants. While most of these events are benign and self-limited, guidelines published by the American Academy of Pediatrics inaccurately identify many patients as higher-risk of a serious underlying aetiology (positive predictive value 5%). Recently, new clinical prediction rules have been derived to more accurately stratify patients. This data were however geographically limited to the USA, with no large studies to date assessing the BRUE population in a different healthcare setting. The study's aim is to describe the clinical management and outcomes of infants presenting to Canadian hospitals with BRUEs and to externally validate the BRUE clinical prediction rules in identified cases., Methods and Analysis: This is a multicentre retrospective study, conducted within the Canadian Paediatric Inpatient Research Network (PIRN). Infants (<1 year) presenting with a BRUE at one of 11 Canadian paediatric centres between 1 January 2017 and 31 December 2021 will be included. Eligible patients will be identified using diagnostic codes.The primary outcome will be the presence of a serious underlying illness. Secondary outcomes will include BRUE recurrence and length of hospital stay. We will describe the rates of hospital admissions and whether hospitalisation was associated with an earlier diagnosis or treatment. Variation across Canadian hospitals will be assessed using intraclass correlation coefficient. To validate the newly developed clinical prediction rule, measures of goodness of fit will be evaluated. For this validation, a sample size of 1182 is required to provide a power of 80% to detect patients with a serious underlying illness with a significance level of 5%., Ethics and Dissemination: Ethics approval has been granted by the UBC Children's and Women's Research Board (H21-02357). The results of this study will be disseminated as peer-reviewed manuscripts and presentations at national and international conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: Neonatal outcome research and clinical follow-up principally focus on neurodevelopmental impairment (NDI) after extremely preterm birth, as defined by the scientific community, without parental input. This survey aimed to investigate parental perspectives about the health and development of their preterm children., Methods: Parents of children aged 18 months to 7 years born <29 weeks' gestational age presenting at a neonatal follow-up clinic over a 1-year period were asked to evaluate their children's health and development. They were also asked the following question: 'if you could improve two things about your child, what would they be?' Responses were analysed using mixed methods. Logistic regressions were done to compare parental responses., Results: 248 parents of 213 children (mean gestational age 26.6±1.6 weeks, 20% with severe NDI) were recruited. Parents evaluated their children's health at a median of 9/10. Parental priorities for health improvements were (1) development, mainly behaviour, emotional health and language/communication (55%); (2) respiratory heath and overall medical fragility (25%); and (3) feeding/growth issues (14%). Nineteen per cent explicitly mentioned 'no improvements'. Parents were more likely to state 'no improvements' if child had no versus severe NDI OR 4.33 (95% CI 1.47 to 12.75)) or if parents had no versus at least a high school diploma (OR 4.01 (95% 1.99 to 8.10))., Conclusions: Parents evaluate the health of their preterm children as being very good, with positive perspectives. Parental concerns outside the developmental sphere should also be addressed both in clinical follow-up and research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Anemia of prematurity is common in extremely preterm neonates, and oxygen exposure may participate to anemia by inhibiting erythropoietin secretion. We aimed to determine whether hyperoxia exerts an independent role in the occurrence of the anemia of prematurity., Methods: Sprague-Dawley pups were exposed to 80% oxygen or room air from days 3 to 10 of life. Main outcome was the difference in hemoglobin and circulating erythropoietin levels in animals exposed to hyperoxia at 10 days of life. We performed a complete blood count analysis using fluorescent laser flow cytometry and measured circulating erythropoietin levels using ELISA., Results: We found lower hemoglobin in the hyperoxia group, compared to the normoxia group, both in males (70 ± 3 versus 78 ± 2 g/l) and in females (71 ± 2 versus 81 ± 3 g/l) at 10 days of life. Reticulocyte count was not increased in the hyperoxia group. Circulating erythropoietin levels were lower at 10 days of life in the animals exposed to hyperoxia, both in males (33 ± 7 versus 73 ± 6 pg/ml) and in females (37 ± 5 versus 66 ± 3 pg/ml), but were similar at 28 days of life., Conclusion: Neonatal exposure to hyperoxia decreases hematopoiesis in rats., Impact: Mechanisms leading to anemia of prematurity are not well known and their study in humans is complicated due to multiple confounders. This study shows for the first time that exposure to high concentrations of oxygen in the neonatal period decreases hematopoiesis in rats, providing insight on the pathophysiological mechanisms of the anemia of prematurity. This research paves the way for future therapeutic developments aiming to reduce the burden of anemia of prematurity and the necessity of red blood cell transfusions in extremely preterm neonates., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To evaluate the association between assisted reproductive technology (ART) and offspring morbidity in the first decade of life., Design: Longitudinal cohort study., Setting: Provincial health registry in Quebec, Canada., Patient(s): A total of 797,654 singleton children born between 2008 and 2019, followed up to 2020., Intervention(s): Retrospective, noninterventional study of any ART procedure vs. no ART., Main Outcome Measure(s): Childhood morbidity, including hospitalization for infectious, allergic, malignant, and other diseases, assessed using adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association with ART. We controlled for unmeasured family-level confounders that were shared among siblings through stratified Cox regression. To do so, we restricted the analysis to 10,097 siblings with discordant exposure to ART and compared the risk of outcomes in exposed vs. unexposed siblings., Result(s): Compared with no ART, ART was associated with 1.23 times the risk of any hospitalization (95% CI 1.19-1.27), 1.25 times the risk of infectious disease hospitalization (95% CI 1.21-1.29), and 1.25 times the risk of allergy hospitalization (95% CI 1.14-1.38). When we used a sibling design to control for shared genetic and environmental confounders, ART was not associated with a greater risk of childhood hospitalization (HR 0.92, 95% CI 0.78-1.08)., Conclusion(s): ART is associated with an elevated risk of hospitalization up to 11 years of age, but discordant sibling analysis suggests that the association may be due to genetic, environmental, or other shared familial confounders., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)